Time to Death and Associated Factors among Tuberculosis Patients in Dangila Woreda,Northwest Ethiopia

Background

Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide. More than 70% of the deaths of TB patients occur during the first two months of TB treatment. The major risk factors that increase early death of TB patients are being positive for human immunodeficiency virus (HIV), being of old age, being underweight or undergoing re-treatment.

Objective

To assess the time of reported deaths and associated factors in a cohort of patients with TB during TB treatment.

Methods

An institution-based retrospective cohort study was analyzed in Dangila Woreda, Northwest Ethiopia from March 1^st through March 30, 2014. All TB patients registered in the direct observed treatment (DOTs) clinic from 2008–2012 were included in the study. Data were entered into EpiData and exported to SPSS for analysis. The survival probability was analyzed by the Kaplan Meier method and Cox regression analysis was applied to investigate factors associated with death during TB treatment.

Results

From a total of 872 cases registered in TB registry log book, 810 were used for the analysis of which 60 (7.4%) died during the treatment. The overall mortality rate was 12.8/1000 person months of observation. A majority of TB deaths 34 (56.7%) occurred during the intensive phase of the treatment, and the median time of death was at two months of the treatment. Age, HIV status and baseline body weight were independent predictors of death during TB treatment.

Conclusions

Most deaths occurred in the first two months of TB treatment. Old age, TB/HIV co-infection and a baseline body weight of <35 kg increased the mortality during TB treatment. Therefore, a special follow up of TB patients during the intensive phase, of older patients and of TB/HIV co-infected cases, as well as nutritionally supplementing for underweight patients may be important to consider as interventions to reduce deaths during TB treatment.     

Exploring disparities between global HIV/AIDS funding and recent tsunami relief efforts: an ethical analysis

Objective: To contrast relief efforts for the 26 December 2004 tsunami with current global HIV/AIDS relief efforts and analyse possible reasons for the disparity. Methods: Literature review and ethical analysis. Results: Just over 273,000 people died in the tsunami, resulting in relief efforts of more than US$10 bn, which is sufficient to achieve the United Nation’s long‐term recovery plan for South East Asia. In contrast, 14 times more people died from HIV/AIDS in 2004, with UNAIDS predicting a US$8 bn funding gap for HIV/AIDS in developing nations between now and 2007. This disparity raises two important ethical questions. First, what is it that motivates a more empathic response to the victims of the tsunami than to those affected by HIV/AIDS? Second, is there a morally relevant difference between the two tragedies that justifies the difference in the international response? The principle of justice requires that two cases similarly situated be treated similarly. For the difference in the international response to the tsunami and HIV/AIDS to be justified, the tragedies have to be shown to be dissimilar in some relevant respect. Are the tragedies of the tsunami disaster and the HIV/AIDS pandemic sufficiently different, in relevant respects, to justify the difference in scope of the response by the international community? Conclusion: We detected no morally relevant distinction between the tsunami and the HIV/AIDS pandemic that justifies the disparity. Therefore, we must conclude that the international response to HIV/AIDS violates the fundamental principles of justice and fairness.     

Anti-tuberculosis therapy-induced hepatotoxicity among Ethiopian HIV-positive and negative patients

Background

To assess and compare the prevalence, severity and prognosis of anti-TB drug induced hepatotoxicity (DIH) in HIV positive and HIV negative tuberculosis (TB) patients in Ethiopia.

Methodology/Principal Findings

In this study, 103 HIV positive and 94 HIV negative TB patients were enrolled. All patients were evaluated for different risk factors and monitored biochemically and clinically for development of DIH. Sub-clinical hepatotoxicity was observed in 17.3% of the patients and 8 out of the 197 (4.1%) developed clinical hepatotoxicity. Seven of the 8 were HIV positive and 2 were positive for HBsAg.

Conclusions/Significance

Sub-clinical hepatotoxicity was significantly associated with HIV co-infection (p = 0.002), concomitant drug intake (p = 0.008), and decrease in CD4 count (p = 0.001). Stepwise restarting of anti TB treatment was also successful in almost all the patients who developed clinical DIH. We therefore conclude that anti-TB DIH is a major problem in HIV-associated TB with a decline in immune status and that there is a need for a regular biochemical and clinical follow up for those patients who are at risk.     

Delay in diagnosis of pulmonary tuberculosis in low-and middle-income settings: systematic review and meta-analysis

Background

Assessment of delays in seeking care and diagnosis of tuberculosis is essential to evaluate effectiveness of tuberculosis control programs, and identify programmatic impediments. Thus, this review of studies aimed to examine the extent of patient, health system, and total delays in diagnosis of pulmonary tuberculosis in low- and middle- income countries.

Methods

It was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Electronic databases were searched to retrieve studies published from 2007 to 2015 including Pubmed central, Springer link, Hinari and Google scholar. Searching terms were pulmonary tuberculosis, health care seeking, health care seeking behavior, patient delay, diagnostic delay, health system delay, provider delay, and doctor delay. Retrieved studies were systematically reviewed and summarized using Comprehensive Meta-analysis software.

Results

Forty studies involving 18,975 patients qualified for systematic review, and 14 of them qualified for meta-analysis. The median diagnostic delay ranged from 30 to 366.5 days [IQR?=?44–77.8], with a 4–199 days [IQR?=?15–50] and 2–128.5 days [IQR?=?12–34] due to patient and health system delays, respectively. The meta-analysis showed 42% of pulmonary tuberculosis patients delayed seeking care by a month or more; uneducated patients [pooled OR?=?1.5, 95%CI?=?1.1–1.9] and those who sought initial care from informal providers [pooled OR?=?3, 95%CI?=?2.3–3.9] had higher odds of patient delay.

Conclusion

Delay in diagnosis is still a major challenge of tuberculosis control and prevention programs in low- and middle- income settings. Efforts to develop new strategies for better case-finding using the existing systems and improving patients’ care seeking behavior need to be intensified.

     

Correlates of Complete Childhood Vaccination in East African Countries

Background

Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination.

Methods

Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette–Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression.

Results

Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries.

Conclusions

Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority.     

The extent of protective footwear use among school-age rural children at high risk for podoconiosis and socio-economic correlates: A household cross-sectional survey in Southern Ethiopia

BackgroundPodoconiosis is preventable if genetically susceptible people wear shoes starting from an early age and do so consistently. However, lack of routine use of footwear is one of the major risk factors for podoconiosis and several other foot-related Neglected Tropical Diseases (NTDs). This study is aimed at describing the extent of footwear use among school-age rural children susceptible to the disease and investigating associated socioeconomic factors.MethodsCross sectional surveys were conducted in 330 randomly selected households in Wolaita zone, southern Ethiopia. A household head and a child aged between 9 and 15 years were recruited from each household. Household heads provided socioeconomic data while children were asked about their footwear ownership and footwear use.ResultsNearly half (49.5%) of the children reported either walking barefoot or wearing under-protective footwear in a range of situations. Girls, older children, those in higher school grades, who belonged to families with higher socio-economic status, and those who owned a larger number of pairs of footwear reported more protective use of footwear. The linear regression model constituting the adequacy of footwear ownership and interaction term (i.e. family socioeconomic status by adequacy of footwear ownership) variables explained 30% of variance in the protective use of footwear (AR² = 0.307). The interaction effect of adequate ownership of footwear and family socioeconomic status consistently predicted the protective use of footwear among children (β = -0.175, p<0.01) though the main effect of adequacy of footwear ownership was stronger (β = 0.507, p<0.001).ConclusionIncreased adoption of protective footwear is needed to effectively prevent school-age children living in endemic areas from developing podoconiosis and other neglected tropical diseases. Interventions aimed to improve the protective footwear use should consider approaches that also increase the socio-economic capacity of families in podoconiosis endemic communities.     

Optimization of ethanol production using newly isolated ethanologenic yeasts

Yeasts are important microorganisms used for ethanol production; however, they are not equally efficient in the amount of ethanol production under different environmental conditions. It is, therefore, necessary to screen for elite strains to utilize them for commercial production of these commodities. In this study, yeasts were isolated from different Ethiopian traditional fermented alcoholic beverages (teji, tella, shamiata and areqe tinisis), milk and ergo, teff and maize dough, soil and compost, flowers, and fruits to evaluate their potential use for ethanol fermentation process. Isolates were screened for efficient ethanol production and the selected ones were identified using phenotypic and genetic characters using D1/D2 region of LSU rDNA sequence analysis. The yeast isolates were evaluated based on their growth and fermentation of different carbon sources. Response surface methodology (RSM) was applied to optimize temperature, pH and incubation time using central composite design (CCD) in Design-Expert 7.0.0. A total of 211 yeasts colonies were isolated of which 60% were ethanologenic yeasts (ethanol producers) and 40% were non-ethanol producers. The yeast population detected from various sources was in the range of 10⁵ CFU from traditional foods and beverages to that of 10³ CFU from fruits and soil samples. The data also showed that the number of colony types (diversity) did not correlate with population density. The highly fermentative isolates were taxonomically characterized into four genera, of which 65% of the isolates (ETP37, ETP50; ETP53, ETP89, ETP94) were categorized under Saccharomyces cerevisiae, and the remaining were Pichia fermentans ETP22, Kluyveromyces marxianus ETP87, and Candida humilis ETP122. The S. cerevisiae isolates produced ethanol (7.6-9.0 g/L) similar with K. marxianus ETP87 producing 7.97 g/L; comparable to the ethanol produced from commercial baker's yeast (8.43 g/L) from 20 g/L dextrose; whereas C. humilis ETP122 and P. fermentans ETP22 produced 5.37 g/L and 6.43 g/L ethanol, respectively. S. cerevisiae ETP53, K. marxianus ETP87, P. fermentans ETP22 and C. humilis ETP122 tolerated 10% extraneous ethanol but the percentage of ethanol tolerance considerably decreased upon 15%. S. cerevisiae ETP53 produced ethanol optimally at pH 5.0, 60 h, and 34^oC. pH 4.8, temperature 36^oC, and 65 h of time were optimal growth conditions of ethanol fermentation by K. marxianus ETP87. The ethanol fermentation conditions of P. fermentans ETP22 was similar to S. cerevisiae ETP53 though the ethanol titer of S. cerevisiae ETP53 was higher than P. fermentans ETP22. Therefore, S. cerevisiae ETP53, K. marxianus and P. fermentans ETP22 are good candidates for ethanol production.     

Regulation of lipid metabolism by Dicer revealed through SILAC mice

Dicer is a ribonuclease whose major role is to generate mature microRNAs, although additional functions have been proposed. Deletion of Dicer leads to embryonic lethality in mice. To study the role of Dicer in adults, we generated mice in which administration of tamoxifen induces deletion of Dicer. Surprisingly, disruption of Dicer in adult mice induced lipid accumulation in the small intestine. To dissect the underlying mechanisms, we carried out miRNA, mRNA, and proteomic profiling of the small intestine. The proteomic analysis was done using mice metabolically labeled with heavy lysine (SILAC mice) for an in vivo readout. We identified 646 proteins, of which 80 were up-regulated >2-fold and 75 were down-regulated. Consistent with the accumulation of lipids, Dicer disruption caused a marked decrease of microsomal triglyceride transfer protein, long-chain fatty acyl-CoA ligase 5, fatty acid binding protein, and very-long-chain fatty acyl-CoA dehydrogenase, among others. We validated these results using multiple reaction monitoring (MRM) experiments by targeting proteotypic peptides. Our data reveal a previously unappreciated role of Dicer in lipid metabolism. These studies demonstrate that a systems biology approach by integrating mouse models, metabolic labeling, gene expression profiling, and quantitative proteomics can be a powerful tool for understanding complex biological systems.